TY - JOUR
T1 - Amelioration of hypertriglyceridemia with hypo-alpha-cholesterolemia in LPL deficient mice by hematopoietic cell-derived LPL
AU - Ding, Yinyuan
AU - Zhang, Ling
AU - Wang, Yuhui
AU - Huang, Wei
AU - Tang, Yin
AU - Bai, Lu
AU - Ross, Colin J.D.
AU - Hayden, Michael R.
AU - Liu, George
PY - 2011/9/29
Y1 - 2011/9/29
N2 - Background: Macrophage-derived lipoprotein lipase (LPL) has been shown uniformly to promote atherosclerotic lesion formation while the extent to which it affects plasma lipid and lipoprotein levels varies in wild-type and hypercholesterolemic mice. It is known that high levels of LPL in the bulk of adipose tissue and skeletal muscle would certainly mask the contribution of macrophage LPL to metabolism of plasma lipoprotein. Therefore, we chose LPL deficient (LPL -/-) mice with severe hypertriglyceridemia as an alternative model to assess the role of macrophage LPL in plasma lipoprotein metabolism via bone marrow transplant, through which LPL will be produced mainly by hematopoietic cell-derived macrophages. Methods and Results: Hypertriglyceridemic LPL -/- mice were lethally irradiated, then transplanted with bone marrow from wild-type (LPL +/+) or LPL -/- mice, respectively. Sixteen weeks later, LPL +/+ →LPL -/- mice displayed significant reduction in plasma levels of triglyceride and cholesterol (408±44.9 vs. 2.7±0.5×10 3 and 82.9±7.1 vs. 229.1±30.6 mg/dl, p<0.05, respectively), while a 2.7-fold increase in plasma high density lipoprotein- cholesterol (p<0.01) was observed, compared with LPL -/-→LPL -/- control mice. The clearance rate for the oral fat load test in LPL +/+ →LPL -/- mice was faster than that in LPL -/-→LPL -/- mice, but slower than that in wild-type mice. Liver triglyceride content in LPL +/+→LPL -/- mice was also significantly increased, compared with LPL -/-→LPL -/- mice (6.8±0.7 vs. 4.6±0.5 mg/g wet tissue, p<0.05, n = 6). However, no significant change was observed in the expression levels of genes involved in hepatic lipid metabolism between the two groups. Conclusions: Hematopoietic cell-derived LPL could efficiently ameliorate severe hypertriglyceridemia and hypo-alpha-cholesterolemia at the compensation of increased triglyceride content of liver in LPL -/- mice.
AB - Background: Macrophage-derived lipoprotein lipase (LPL) has been shown uniformly to promote atherosclerotic lesion formation while the extent to which it affects plasma lipid and lipoprotein levels varies in wild-type and hypercholesterolemic mice. It is known that high levels of LPL in the bulk of adipose tissue and skeletal muscle would certainly mask the contribution of macrophage LPL to metabolism of plasma lipoprotein. Therefore, we chose LPL deficient (LPL -/-) mice with severe hypertriglyceridemia as an alternative model to assess the role of macrophage LPL in plasma lipoprotein metabolism via bone marrow transplant, through which LPL will be produced mainly by hematopoietic cell-derived macrophages. Methods and Results: Hypertriglyceridemic LPL -/- mice were lethally irradiated, then transplanted with bone marrow from wild-type (LPL +/+) or LPL -/- mice, respectively. Sixteen weeks later, LPL +/+ →LPL -/- mice displayed significant reduction in plasma levels of triglyceride and cholesterol (408±44.9 vs. 2.7±0.5×10 3 and 82.9±7.1 vs. 229.1±30.6 mg/dl, p<0.05, respectively), while a 2.7-fold increase in plasma high density lipoprotein- cholesterol (p<0.01) was observed, compared with LPL -/-→LPL -/- control mice. The clearance rate for the oral fat load test in LPL +/+ →LPL -/- mice was faster than that in LPL -/-→LPL -/- mice, but slower than that in wild-type mice. Liver triglyceride content in LPL +/+→LPL -/- mice was also significantly increased, compared with LPL -/-→LPL -/- mice (6.8±0.7 vs. 4.6±0.5 mg/g wet tissue, p<0.05, n = 6). However, no significant change was observed in the expression levels of genes involved in hepatic lipid metabolism between the two groups. Conclusions: Hematopoietic cell-derived LPL could efficiently ameliorate severe hypertriglyceridemia and hypo-alpha-cholesterolemia at the compensation of increased triglyceride content of liver in LPL -/- mice.
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U2 - 10.1371/journal.pone.0025620
DO - 10.1371/journal.pone.0025620
M3 - Article
C2 - 21980507
AN - SCOPUS:80053340224
SN - 1932-6203
VL - 6
JO - PloS one
JF - PloS one
IS - 9
M1 - e25620
ER -